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Article: Four Viruses! Alter Paper Confirms Retroviral Findings in CFS

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How can we help Cort make this a better forum?
Now for the practical considerations: Cort, HOW do you want people to bring up factual errors? Would it be helpful if people took the time to rewrite a contested segment? Or do you just want a succinct bullet list detailing the error that you can wordsmith? Do you want the first comments through PM's? Will you respond to them? What are some tangible ways that members can make it easier for you to be willing to address errors? What are some tangible ways that we can make it easier for you to incorporate edits when factual errors are identified? Would it be helpful to have a "how you can help me" segment in Nuts and Bolts? Other than the obvious issue of addressing tone on both sides, is there something that would make this process of continuous improvement happen more swiftly and easily, so that seriously ill patients giving feedback aren't also burned out by the process?
I appreciate this question and it is an important one. My guess is that we will all be stepping a bit more into the limelight as time goes and as XMRV gets definitively associated. The PR Forums are the biggest ME/CFS Forums on the internet - the increase in registrations over the past month has just been incredible - and as XMRV gains traction I imagine that will increase.

Anyway, it will be more and more important that we, of course including myself, get things right. I do see the comment mechanisms on the Articles as a good way of doing that. As I noted I have altered about five parts of the paper in response to comments. I think this is an example of using the collective experience on the Forums in a good way..the system works. I am the editor - so I do ultimately do decide - but I generally decide in favor of peoples suggestions.

PM's are fine as well although I like the idea of things being transparent and everybody getting a look at them. Whatever anyone is comfortable with. Generally when I put an article I check it repeatedly during the day so I can pick up comments pretty quickly.

Thanks Sunshine for that great analysis - I think it represented my feelings about the Forums and how those can cause friction. It'll be interesting to see how the subset question plays out with XMRV and what happens to the name of this disorder, etc. - there will be some big changes in store - here, probably and elsewhere.
 
FWIW I'll have a quick go at posting what I wanted to say about the study since I haven't had a chance to post reflections on the issues raised by the Alter study all week and I've now lost the window to do a whole lot of other cool stuff I had lined up...

What strikes me is the bizarre possibility that the results might actually mean what they say. I'm not talking about the negative studies for now, other than the CDC's negative study...

The WPI study required neurological symptoms, CCC, Fukuda, and severe disability. Unless I'm mistaken, the patients Alter studied were basically Fukuda.

XMRV is neurophilic (seeks out and infects nerve tissue) but are the other MLVs? I really don't know, but could they differ in this respect - that the others aren't neurophilic?

Is it possible that the Alter patients did not have the severe neurological symptoms that WPI studied?

If it were, then we are seeing what looks very much like: WPI studied ME, Alter studied CFS, as completely discrete groups.

It would fit extremely well with a certain point of view:
ME = severe, neurological = XMRV
CFS = related, no neurological symptoms = MLVs.

The ME patients probably have the MLVs as well, as the WPI are now finding.

With this theory, still fine, and no problem with Alter failing to detect XMRV.

Now: what about the CDC's 0/0?

As has previously been commented, if you had a background level of 1% in the general population, you've got a 35% chance of finding nothing at all in the samples they tested.

Bear in mind though: this assumes 100% test accuracy. We have no clue how much that may vary in this case. So if you had a test that would have caught 50% of them, you'll still get the odds above if the population infection rate is 2% - 35% chance to find nothing.

But still: from all the above, this would mean to say that the CDC population, also, would have to be completely distinct: none of them have ME or CFS. They have TATT (tired all the time), best assessed over the phone.

Well. The thing that then jumps out is: all of these findings are exactly what the major controversy has been all about! And here we have 3 discrete teams of researchers, with 3 different definitions, finding 3 different things - results which fit our overall hypothesis frankly!

So why are we het up?

Because they fall so extraordinarily well into the 3 chunks we would predict.

We would have assumed that there would at least be one or two ME and one or two CFS patients in the CDC survey. But none? Once again, and as with the 0/0 studies, the starkness of the results just seems incredible - it can't be a valid test, surely?

In the case of the CDC, at least, Dr Vernon may very well be right: they designed the test to fail. But maybe that really means to say, in reality: didn't try especially hard. Maybe a weak association would have been acceptable.

Maybe we can layer a completely discrete subset of patients over the top of a faulty methodology and say: it was both!

Again: it is not surprising; again it is what we have said.

They are not studying ME/CFS patients anyway, and even if they were, they aren't up to testing them properly. And of course not - if they are a discrete population of psychologists studying a discrete population of TATT.

Now then: a conspiracy theory can be added in too if you like, or not, as you choose, because the CDC with awareness of the above would be well-advised to position their patient group as the CFS, which stays as CFS, and is the people who don't have ME/CFS (XMRV and the MLVs). The CDC want to keep the TATT - 10% f the population - for the next round of CBT-based control, and they will call them CFS still because the XMRV and MLV+ populations will get a new disease and be out the door.

So maybe CDC really had no ME/CFS patients, or maybe they were pretty sure they hadn't but didn't want to risk that even their lot had XMRV so they made sure of it with a bogus test as well. Belt and braces, as we say.

We still have the XMRV population level and the 3 negative papers to explain, so I think there will some more to it than this, but this is the obvious picture which seems to emerge to me.

It's kind of a picture where everybody was right, all shall win, and all shall have prizes...although of course that isn't necessarily a reason to trust it...
 
The bottom line is this:

Cort does not believe CFS is a single neurological disease caused by one agent. Cort does promote stories about 'recovery' in CFS which goes against current medical knowledge about neuro immune disease. CFS, however, is not a neuro immune disease, (look at the diagnostic criteria). Cort is free to do this, it's his website not anyone elses. CFS includes people with unspecific reasons for having CFS. This is understandable. This is Cort's reason for his articles written supporting biopsychosocial explanations of CFS. It's Cort's decision.

Sunshine,

Thank you for taking the time to put into words what I have long felt has been a central issue with "CFS" and a central (unacknowledged) issue/challenge faced by the CAA.

I was originally Dx with "some variant of CFS" by Dr. Montoya in 1994. I was working in health research at the time and knowing what I did about cohorts and signal to noise ratios I refused the "CFS" label because it was hopelessly confused in both the clinical and research worlds. Over 16 years later I still very careful to only use the term "CFS" as short hand amongst those to whom it means something very specific (neuro-immune CFS or ME).

From my personal experience, getting my emotional/psychological house in order has been both important and beneficial but not because I suffer from a psychological or emotional disorder but because my physical and emotional states are connected. At best, everyday I'm getting by with very few resources to spare and whether it's physical or emotional, I can't keep going to the well with out draining it. It's just not that deep.

And so, regardless of the disease processes I am having to deal with, emotional and psychological house keeping is important to me (and it doesn't imply anything about etiology, nor does it promise a cure).

I do think that the retroviral research holds great promise and at the same time it presents a threat. I'm not worried about the people for whom a test is developed and treatment is made available. I am more concerned with what we as a community do with those that suffer from an organic illness and for whom the big break through is not just around the corner. From my perspective, CFS is far to loosely applied (and I suspect that the cohorts of the two positive studies to date are far to similar) for there to be a one size fits all answer, even for all of those who are amongst the sickest amongst us.

And yes, we have the CDC to thank for the pitiful state of "CFS" that we all have to contend with everyday.
 
They have talked of variants, not different viruses. They have also made it quite clear that this is less than the normal variation found within a single strain of HIV. The title is incorrect and misleading.

The point you make about variation is true but misleading in this context, because there are other differences between the MLVs and XMRV which are high percentages, however maybe somebody else can dig back for that detail, I have to log off now.

But: whether they are separate viruses, or strains, sufficient to justify naming separately and splitting off, is indeed the moot point, because it appears that the WPI have been achieving similar results in parallel and crucially (here is what I think you should be asking): would Dr Alter have called it all 'XMRV' back in February, or in May when he presented the slides?

I seem to remember one of the bulletpoints (please somebody check) said he was finding "XMRV and related MLVs". Did that quote come from that source?

So if he's presenting that differently now, then that is the change that has happened in the 3 months of silence. And those bullet points are what need checking. I suspect it is like that: present the state of the science 9 months further on, and thus present it as something different, to dampen down the impact and undermine the WPI's position.

It's also right to point out that the WPI are undermined by the situation now as on the face of it from the headline findings of the two papers, if one assumes Alter's more reliable (people will) it looks as though the WPI were claiming "XMRV" and "CFS" when they actually found a range of MLVs similar to XMRV in a tightly defined subgroup of CFS patients - the issue would then be that they overinterpreted their findings and misled everyone. I think that's completely unfair, but that's the way that narrative seems to point, and that's what the dispute here seems to have been about.
 
The point you make about variation is true but misleading in this context, because there are other differences between the MLVs and XMRV which are high percentages, however maybe somebody else can dig back for that detail, I have to log off now.

But: whether they are separate viruses, or strains, sufficient to justify naming separately and splitting off, is indeed the moot point, because it appears that the WPI have been achieving similar results in parallel and crucially (here is what I think you should be asking): would Dr Alter have called it all 'XMRV' back in February, or in May when he presented the slides?

I seem to remember one of the bulletpoints (please somebody check) said he was finding "XMRV and related MLVs". Did that quote come from that source?

So if he's presenting that differently now, then that is the change that has happened in the 3 months of silence. And those bullet points are what need checking. I suspect it is like that: present the state of the science 9 months further on, and thus present it as something different, to dampen down the impact and undermine the WPI's position.

It's also right to point out that the WPI are undermined by the situation now as on the face of it from the headline findings of the two papers, if one assumes Alter's more reliable (people will) it looks as though the WPI were claiming "XMRV" and "CFS" when they actually found a range of MLVs similar to XMRV in a tightly defined subgroup of CFS patients - the issue would then be that they overinterpreted their findings and misled everyone. I think that's completely unfair, but that's the way that narrative seems to point, and that's what the dispute here seems to have been about.

What it is important to get out of all of this is that the paper brought into question the "xenotropic" component of the nomenclature. They are all MuLVs, and from what I understood, they are not even necessarily different strains - more research is needed there because they were only partially sequenced. Variants is, for now, the best description, strain is not, and it is not correct to call them different viruses. Even within a single person and over time, retroviruses mutate, and the normal level of mutation is consistent with the level of variation they have found. During that process, the virus could certainly recombine, within a single host, to create a variant that is xenotropic. What the Alter paper showed is that the xenotropic variant is not the whole picture.
 
For those of you who remember the alka-seltzer commercials, I think we should start awarding T-shirts which say, "I can't believe I read the whole blog" for anyone who actually got through the 290 or so comments.

The obvious problem with this illness is that we don't know what we have and how to treat it. Some of us have low NK activity and immune dysfunction, some low blood volume and autonomic dysfunction, some have significant neurological issues, some endocrine dysfunction and other sleep dyfunction. Most of us have a combination of those factors and have been placed under the all knowing CFS monicker to define our illness. That being said, EVERYONE on this site has a physiological based illness.

In my view, Sunshine said it best, "The only way to stop irritation on both sides, is for there to be a diagnostic test for CFS, or for a neuro immune disease linked to XMRV/MULV."

Until then, many of you may want to stop shooting the messenger. So far in reading the comments, Cort has been called ignorant, biased, sexist, told he doesn't know what he's talking about, that he has an agenda and that he may have an independence issue/conflict of interest as a paid "consultant". This is America so everyone gets an opinion but all the article really said in summary was that after three negative studies, the Alter study confirmed the findings of WPI and in a statistically significant result, showed evidence of a family of retrovirus in the samples tested which were close cousins of XMRV. I recognize that many of you are angry at the CDC, the government and certain physicians and have sensitivities toward various groups that you may have relationships with but the displacement on Cort is completely unwarranted.

We've got highly respected scientists dealing with these studies who can't replicate findings or agree on the intepretation of the results. Whether Cort's interpetation of complex science is perfect is completely irrelevant to the big picture. The way I see it, Cort's only agenda is to get well himself, help and meet others along the way of his journey and create a voice for people with our illness (or reasonably similar disease pattern) to be heard and share information between. I think it's fine that we have some highly educated individuals with medical and scientific training on the board who can provide insight into the research but at the end of the day, it's all just a dog and pony show until science figures this out.
 
For those of you who remember the alka-seltzer commercials, I think we should start awarding T-shirts which say, "I can't believe I read the whole blog" for anyone who actually got through the 290 or so comments.

The obvious problem with this illness is that we don't know what we have and how to treat it. Some of us have low NK activity and immune dysfunction, some low blood volume and autonomic dysfunction, some have significant neurological issues, some endocrine dysfunction and other sleep dyfunction. Most of us have a combination of those factors and have been placed under the all knowing CFS monicker to define our illness. That being said, EVERYONE on this site has a physiological based illness.

In my view, Sunshine said it best, "The only way to stop irritation on both sides, is for there to be a diagnostic test for CFS, or for a neuro immune disease linked to XMRV/MULV."

Until then, many of you may want to stop shooting the messenger. So far in reading the comments, Cort has been called ignorant, biased, sexist, told he doesn't know what he's talking about, that he has an agenda and that he may have an independence issue/conflict of interest as a paid "consultant". This is America so everyone gets an opinion but all the article really said in summary was that after three negative studies, the Alter study confirmed the findings of WPI and in a statistically significant result, showed evidence of a family of retrovirus in the samples tested which were close cousins of XMRV. I recognize that many of you are angry at the CDC, the government and certain physicians and have sensitivities toward various groups that you may have relationships with but the displacement on Cort is completely unwarranted.

We've got highly respected scientists dealing with these studies who can't replicate findings or agree on the intepretation of the results. Whether Cort's interpetation of complex science is perfect is completely irrelevant to the big picture. The way I see it, Cort's only agenda is to get well himself, help and meet others along the way of his journey and create a voice for people with our illness (or reasonably similar disease pattern) to be heard and share information between. I think it's fine that we have some highly educated individuals with medical and scientific training on the board who can provide insight into the research but at the end of the day, it's all just a dog and pony show until science figures this out.

That was one good post. Hats off.
 
Its possible but hardly likely that both findings are correct. If retroviruses are usually found in swarms even within the same persons body then it seems more likely that both groups are missing part of the swarm. Dr. Alter reported, in fact, that WPI researchers were finding more variation over time. Cort's blog

Cort's post
You missed my point in fact you missed an entire sentence; ie 'both groups are missing part of the swarm'- is that incorrect?. I'm trying to say two things - both are right and both are wrong....I'm not saying the WPI is wrong about XMRV - I meant to say that the WPI missed the MLV's (as it turns they haven't - they just didn't report on them, but they are in their patent application) and that the Alter group missed XMRV...

I'm not saying XMRV is not there! There are magnitudes more evidence for XMRV being there than the MLV's. they were able to grow it, find antibodies to it, etc - as I pointed out in my paper. You have negative interpretations of alot of statements - that I had never thought of.

You can't help but be divisive can you? - Hence the comment comparing me to Trish Tsoudero's. I end up gnashing my teeth over the innuendo's that pepper your posts. I/m trying to work with you - I have altered parts of the paper to assist you and I'm put in the same box as Myra McClure and Trish Tsouderos! Nice!

If I quoted the entire section I missed nothing. If you meant to say something, then say it. You should not post a blog which purports to tell the truth when you have not checked your facts, and have not communicated what you meant to say. In reality you said that one of the studies must be wrong. This is not the opinion of those who conducted the studies. If you want to say one of them must be wrong at least quote someone qualified to say such a thing. In this case it would be Myra McClure. But why would you ever do that.

You question my negative interpretations that you had not thought of. This is precisely why you should check and polish before posting, or don't post at all. It is not fair to spread false, incorrect, negative information. Lives are at stake, literally.

There is no innuendo in my posts. I say what I mean.

Now people have been talking about the psych lobby and everyone else. The truth is that there is the psych lobby, there are those who support the psych lobby, there are those who help the psych lobby, there are those who have no idea, there are those who help the biomedical researchers, there are those who support the biomedical researchers, and there are the biomedical researchers. And plenty more. Any article that spreads incorrect information, or negatively alters the interpretation of the results, is helping the psych lobby. We cannot afford to do that. If this helps just one patient, we have to stick to the science, nothing more.

As for the Lo et al. cohort, there were two sets of patients, Fukuda and Holmes.

CFS does not exist, only ME patients in CFS who cannot be diagnosed with ME. These viruses have been found in those patients. CFS is a creation of the psych lobby. However, the CDC had everyone trapped in the CFS creation, they have no out, they dropped the ball, deliberately.

Finally, we leave no one behind. We force a change thorough so that this can never happen again.
 
A post about sexism in general.

I grew up when Margaret Thatcher was Prime Minister. In the last four years we had Blair's babes. Sexism, whether intentional or not, is alive and well. (This is nothing to do with Cort, like Awol I have no reason to believe he is sexist)
 
Holmes criteria

Mark and anybody else interested.

The 25 Komaroff patients satisfied the Holmes Criteria (below). 21 satisfied the Fukuda criteria

Holmes Criteria

I. New onset of persistent or relapsing fatigue, with at least 50%
reduction of activity level for at least 6 months.

II. Exclusion of other conditions through History, Physical examina-
tion and Laboratory Examination.

III. 6 of the following 11 symptoms:

1. Mild fever
2. Sore throat
3. Painful lymph nodes
4. Muscle weakness
5. Muscle pain
6. Prolonged fatigue after exercise
7. Headaches
8. Joint pain
9. Neuropsychologic complaints
10. Sleep disturbance
11. Acute onset of symptoms

And 2 of 3 signs on physical examination:

1. Low grade fever
2. Throat inflammation
3. Palpable or tender lymph nodes

IV. Or 8 of the 11 symptoms without physical signs.

I have only started following the research closely in the last four or five years but my vague impression is that the Holmes definition and perhaps in particular Komaroff patients were pretty "neurologic" e.g. abnormalities on brain scans.
 
We've got highly respected scientists dealing with these studies who can't replicate findings or agree on the intepretation of the results.

Hi. Please note that no negative study on XMRV in CFS has ever used the same scientific methods that the Lombardi group used. This is very important to remember. When someone cannot 'find' XMRV (Groom, Kupperveld etc) it would help if they actually followed the same methods as the WPI.

Alter, however, replicated the WPI findings, but not the method proving though it can be done. Alter himself stated:

''Why Have Other Studies Come to Different Conclusions? Although we find evidence of a broader group of MLV-related viruses, rather than just XMRV, in patients with CFS and healthy blood
donors, our results clearly support the central argument by Lombardi et al. (3) that MLV-related viruses are associated with CFS and are present in some blood donors.''


Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome
and healthy blood donors. www.pnas.org/cgi/doi/10.1073/pnas.1006901107

SCIENCE agree, they commented on the Alter/Lo paper.............

''The study confirms a controversial 2009 paper that reported CFS patients are often infected with the virus, called XMRV.''

SCIENCEMAG.ORG VOL 329. August 26, 2010. Chronic Fatigue Syndrome. New XMRV Paper Looks Good, Skeptics Admit - Yet Doubts Linger. Author Martin Enserink. Published by AAAS

So respected or not, the people who fail to detect XMRV/MULV cannot do their science very well or they'd have found XMRV/MULV. Think back to the comments of CAA's Suzanne Vernon who revealed the CDC didn't even use the correct tubes to store the blood in, or that the British study used water as a control sample and both had no known positive sample, to test if their research even worked and their conclusions were scientifically valid! :Retro redface: This anomoly is highly unprofessional, and usually stops a paper from being published. For political reasons, the publication went ahead. Indeed the negative XMRV paper in PLoS ONE by Wessely/McClure was paid for to be published. :ashamed:

There's a good video here on youtube explaining the Alter/Lo paper for people who may be confused if XMRV is a 'different' virus to MULV's, not possible as it is an MULV.

http://www.youtube.com/watch?v=9ZEwQUg7o6I
 
XMRV - L'Agent du Jour - quote from Dr Alter/slide at Zagreb conference

and crucially (here is what I think you should be asking): would Dr Alter have called it all 'XMRV' back in February, or in May when he presented the slides?

I seem to remember one of the bulletpoints (please somebody check) said he was finding "XMRV and related MLVs". Did that quote come from that source?

So if he's presenting that differently now, then that is the change that has happened in the 3 months of silence. And those bullet points are what need checking. I suspect it is like that: present the state of the science 9 months further on, and thus present it as something different, to dampen down the impact and undermine the WPI's position.


Mark is absolutely right and its exactly the same thing has been nagging at the back of my mind since the Alter/Lo publication this week. The crucial point is that Dr Alter specifically said (according to the Dutch journalists) that he had found "XMRV & MLV's" at his Zagreb presentation (?in May/June).

I have been looking in all the obvious places, but was only able to relocate the original Dutch journalists’ article from June 22nd 2010 today.

Here it is and the quote from Dr Alter is quite specific and very clear: “XMRV and related MLV’s are in the donor supply ..”

http://www.mmdnewswire.com/xmrv-9040.html

"The data in the Lombardi, et al Science manuscript are extremely strong and likely true, despite the controversy", was one comment on the XMRV findings reported by Alter in Zagreb. "Although blood transmission to humans has not been proved, it is probable. The association with CFS is very strong, but causality not proved. XMRV and related MLVs are in the donor supply with an early prevalence estimate of 3%‐7%. We (FDA & NIH) have independently confirmed the Lombardi group findings."

So either Dr Alter was:
1) referring to the WPI’s finding with this XMRV comment, or
2) he has been misquoted (does anyone have those original slides from his Zagreb lecture please? - these were confirmed as being genuine by a spokeswoman for either the NIH or the FDA at the time), or
3.) he is not presenting the full extent of the facts in his PNAS article (I did have another much more tactful phrase for this, but it has slipped my mind at time of writing!)
4.) He says specifically that XMRV is also in the 'donor supply' ie implying the blood bank (not just MLV,s)
5.) I have misunderstood entirely and this has already been covered in the forum discussions.

The title I have after my forum name (above) is “XMRV: L’Agent du Jour”. I have this because it is a direct quote from one of Dr Alter’s slides/his speech at the June Zagreb conference and it really appealed to me at the time. If he had said it differently, my title would have been "MLV"!

WHAT is going on here?
And does anyone have those slides please?

Apologies if this has already been resolved.
 
XMRV and related MLVs are in the donor supply with an early prevalence estimate of 3%‐7%. We (FDA & NIH) have independently confirmed the Lombardi group findings."

So either Dr Alter was:
1) referring to the WPIs finding with this XMRV comment, or
My guess is 1 because of the percentages - combining the two studies (even though I know it is 3.7% which should round to 4%) (or maybe combining more studies given there have been others and doing some rounding).
 
Hi Dolphin. It's in the Alter PNAS paper, page 6. To quote the authors.........



1988 is Holmes definition.
1994 is Fukuda definition.

Peace.
;)
The paper says:
Each of the 25
patients was systematically evaluated with a standardized history (supplemented
by a patient questionnaire), physical examination, and battery of
laboratory tests. Each met the 1988 CDC criteria for CFS, and 21 also met the
1994 CDC criteria.
But just to be sure 25+21=46 i.e. too many.

I have not seen any subgroup analysis or any other evidence to suggest:
V99 said:
As for the Lo et al. cohort, there were two sets of patients, Fukuda and Holmes.

Peace.
;)
 
Huh?

You said to V99 where is the evidence of Holmes criteria, right?

So I posted a quote on V99's behalf from the Alter paper showing two criteria were used (one being Holmes).

V99 is saying there are two sets of patients who both meet, both criteria. Which is your point also.

Maybe we are at crossed purposes here?
 
Huh? You've repeated my reply I first gave.

You said to V99 where is the evidence of Holmes criteria, right?

So I posted a quote from the Alter paper showing two criteria were used (one being Holmes) and you reply saying there were two criteria used.

:confused:
I queried this statement:
V99 said:
As for the Lo et al. cohort, there were two sets of patients, Fukuda and Holmes.
To me, that reads that there was set of patients A that satisfied Fukuda and set of patients B that satisfied Holmes and some comparison was made between them and/or we are given separate information on them.

There were different sets of patient e.g. there were the Komaroff patients and the rest. But that statement implies something else to me.
The 25 Komaroff patients were required to satisfy the Holmes criteria. When one looks at them, 21 satisfied the Fukuda. But there is no analysis that I know of that comparied the Holmes+Fukuda patients (n=21) and the Holmes\Fukuda (Holmes but not Fukuda) patients (n=4). The Fukuda reference was just in passing as far as I know.
 
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